We located hepatic lipase in liver, both extravascularly and on the vascular endothelium with two antibodies to purified hepatic lipase. That two different antibodies identify hepatic lipase in two different sites in liver suggests each may be recognizing different isotopes of the lipase specific to each site. Combined lipase deficient (cld/cld) mice have functional deficiencies of both lipoprotein lipase and hepatic lipase. We located hepatic lipase and lipoprotein lipase in cld/cld livers and cultured hepatocytes and found that hepatic lipase is present extracellularly while lipoprotein lipase accumulates within hepatocytes. It appears that the intracellular processing of these two non-functional glycoproteins is different in hepatocytes from cld/cld mice. Niemann-Pick Type-C (NP-C) disease is a cholesterol storage disorder in which unesterified cholesterol derived from LDL accumulates intracellularly in lysosomes and Golgi. The relative distribution of LDL-derived cholesterol in Golgi compartments of normal and NP-C fibroblasts incubated with LDL for 24 hours was determined with freeze-fracture cytochemistry. Filipin complexes with cholesterol, forming characteristic deformations in Golgi membranes which can be quantitated. The highest density of membrane deformations in normal fibroblasts was present in Golgi condensing vacuoles and that in NP-C fibroblasts was in Golgi trans cisternae. Golgi condensing vacuoles of normal fibroblasts had more membrane deformations than those of NP-C fibroblasts indicating that translocation of cholesterol to condensing vacuoles is deficient in mutant cells. Impaired transport of cholesterol through Golgi to condensing vacuole membranes could explain the defective mobilization of cholesterol and transport to the plasma membrane in NP-C cells. The cellular location of perilipin, an adipocyte specific phosphoprotein, was studied with electron microscopic immunocytochemistry in cultured 3T3- L1 adipocytes. Membrane leaflets of endoplasmic reticulum were continuous with the monolayer in contact with the lipid droplet core. Immunogold labeling for perilipin was found on the surface monolayer in contact with the lipid droplets and also within cisternae of the surrounding endoplasmic reticulum. These results indicate that perilipin is located on the leaflet of endoplasmic reticulum surrounding lipid droplets.